Félix Recillas-Targa

Intereses de Investigación

Our group is concerned with the relationship between chromatin structure and the regulation of gene expression during development. The development of an organism is a consequence of coordinated regulation of gene expression. Higher eukaryotic genomes are assembled into chromatin. Chromatin is composed of histones, which form structures known as nucleosomes that interact with DNA, generating the first level of DNA compaction inside the cell nucleus. At the present time it is generally accepted that chromatin structure represents one of the first levels of regulation of gene expression during development. Proper timing and spatial expression of a gene or group of genes requires a coordinated remodeling of chromatin structure to allow the transcriptional machinery to access target sequences in the DNA. Our laboratory is interested in understanding the effects of chromatin structure on gene regulation at distinct levels, ranging from regulatory elements to chromatin domain formation and maintenance. We are using the chicken alpha- and beta-globin domains as experimental systems. To address different questions, the laboratory projects combine molecular and cellular techniques.

Premios y distinciones

Líneas de Investigación

Chromatin structure and mechanisms of action of regulatory elements located at the 3 side of the chicken alpha-globin domain : For several years we have been working on the characterization of the silencer-enhancer elements located at the 3 side of the chicken alpha-globin domain. Several models had been proposed to describe their mechanisms of action. At the present time it remains unclear how these elements regulate gene expression during development. It is less clear if the domain and the chromatin structure of these elements can influence their regulatory functions.We are currently investigating the relationship between those long-distance regulatory elements and their chromatin structure. We have recently studied the role of DNA methylation and DNA demethylation in erythroid differentiation in this locus and performed Chromosome Conformation Capture (3C) experiments to understand the topological role of the long distance regulatory elements of the locus during development. Furthermore, ChIP-seq experiments have been peformed using different antibodies against nuclear factors to further understand our initial prediction in which the chromatin structure of such elements plays a critical role in their developmentally regulated action.

Epigenetic regulation of human tumor suppressor genes, microRNAs promoters, long non-coding and antisense RNAs : Abnormal epigenetic silencing of CpG-islands corresponding to tumor suppressor gene promoters appears to be a more frequent phenomenon in tumorigenesis than was previously anticipated. Evidence from our laboratory leads us to suggest a novel contribution of methylation-sensitive nuclear factors on tumor suppressor promoter regulation and protection against abnormal DNA methylation. More recently, we have been interested on member of Polycomb and Trithorax group of proteins and their influence over tumor suppressor gene regulation. We have recently studied the role of the antisense RNA Wrap53 and CTCF in the regulation of the human p53 tumour suppressor gene. These aspects are also studied in diverse microRNAs and long non-coding RNAs in tumor cell lines.

Chromatin domain formation, position effects and chromatin boundaries : The chicken alpha- and beta-globin domains are two of the best-characterized developmentally regulated groups of genes. The organization of the genome into discrete structural and functional domains is increasingly recognized as one of the first steps in the regulation of gene expression. We would like to understand the contribution of boundary or insulator elements to domain formation and maintenance. In addition, we are interested in the capacity of insulator elements to protect a transgene against variability in expression, known as position effects, due to distinct integration sites in the genome. This property of insulator elements should be very useful in gene therapy protocols

In vivo studies of the multifunctional nuclear factor CTCF : We have recently adopted the fruit fly Drosophila melanogaster as a biological system model to study the role of CTCF during early development and in certain signal transduction pathways taking advantage of loss and gain of function approaches. Furthermore and in collaboration with Ernesto Maldonado we would like to describe the distribution of CTCF and better understand its role during zebrafish development.